Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL0JH2C)

• DOT Name: Zinc finger protein ubi-d4 (DPF2)
• Synonyms: Apoptosis response zinc finger protein; BRG1-associated factor 45D; BAF45D; D4, zinc and double PHD fingers family 2; Protein requiem
• Gene Name: DPF2
• Related Disease:
  Coffin-Siris syndrome
  Acquired aplastic anemia
  Adult glioblastoma
  Coffin-Siris syndrome 1
  Coffin-Siris syndrome 7
  Glioblastoma multiforme
  Glioma
  Influenza
  Intellectual disability
• UniProt ID: REQU_HUMAN
• PDB ID: 3IUF; 5B79; 5VDC; 6LTH; 6LTJ
• Pfam ID: PF14051 ; PF00628
• Sequence:
  MAAVVENVVKLLGEQYYKDAMEQCHNYNARLCAERSVRLPFLDSQTGVAQSNCYIWMEKR
  HRGPGLASGQLYSYPARRWRKKRRAHPPEDPRLSFPSIKPDTDQTLKKEGLISQDGSSLE
  ALLRTDPLEKRGAPDPRVDDDSLGEFPVTNSRARKRILEPDDFLDDLDDEDYEEDTPKRR
  GKGKSKGKGVGSARKKLDASILEDRDKPYACDICGKRYKNRPGLSYHYAHSHLAEEEGED
  KEDSQPPTPVSQRSEEQKSKKGPDGLALPNNYCDFCLGDSKINKKTGQPEELVSCSDCGR
  SGHPSCLQFTPVMMAAVKTYRWQCIECKCCNICGTSENDDQLLFCDDCDRGYHMYCLTPS
  MSEPPEGSWSCHLCLDLLKEKASIYQNQNSS
• Function: Plays an active role in transcriptional regulation by binding modified histones H3 and H4. Is a negative regulator of myeloid differentiation of hematopoietic progenitor cells. Might also have a role in the development and maturation of lymphoid cells. Involved in the regulation of non-canonical NF-kappa-B pathway.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coffin-Siris syndrome	DIS8L03H	Definitive	Autosomal dominant	[1]
Acquired aplastic anemia	DISCMKMX	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Coffin-Siris syndrome 1	DIS95FRP	Strong	CausalMutation	[4]
Coffin-Siris syndrome 7	DISZGBZ8	Strong	Autosomal dominant	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Influenza	DIS3PNU3	Strong	Biomarker	[5]
Intellectual disability	DISMBNXP	Strong	Biomarker	[4]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Zinc finger protein ubi-d4 (DPF2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Zinc finger protein ubi-d4 (DPF2).	[7]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Zinc finger protein ubi-d4 (DPF2).	[9]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Zinc finger protein ubi-d4 (DPF2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Zinc finger protein ubi-d4 (DPF2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Zinc finger protein ubi-d4 (DPF2).	[13]

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Zinc finger protein ubi-d4 (DPF2).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Zinc finger protein ubi-d4 (DPF2).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Zinc finger protein ubi-d4 (DPF2).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Zinc finger protein ubi-d4 (DPF2).	[8]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Zinc finger protein ubi-d4 (DPF2).	[14]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] SWI/SNF subunit expression heterogeneity in human aplastic anemia stem/progenitors.Exp Hematol. 2018 Jun;62:39-44.e2. doi: 10.1016/j.exphem.2018.03.005. Epub 2018 Mar 27.
• [3] The aberrant splicing of BAF45d links splicing regulation and transcription in glioblastoma.Neuro Oncol. 2018 Jun 18;20(7):930-941. doi: 10.1093/neuonc/noy007.
• [4] Mutations in the BAF-Complex Subunit DPF2 Are Associated with Coffin-Siris Syndrome. Am J Hum Genet. 2018 Mar 1;102(3):468-479. doi: 10.1016/j.ajhg.2018.01.014. Epub 2018 Feb 8.
• [5] Double Plant Homeodomain Fingers 2 (DPF2) Promotes the Immune Escape of Influenza Virus by Suppressing Beta Interferon Production.J Virol. 2017 May 26;91(12):e02260-16. doi: 10.1128/JVI.02260-16. Print 2017 Jun 15.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [10] Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [14] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.